0 12 Microtubules Microtubule NNP 13 20 mediate mediate VBP 21 29 cellular cellular JJ 30 47 25-hydroxyvitamin 25-hydroxyvitamin NN 48 50 D3 d3 NN 51 62 trafficking trafficking NN 63 66 and and CC 67 70 the the DT 71 78 genomic genomic JJ 79 87 response response NN 88 90 to to TO 91 112 1,25-dihydroxyvitamin 1,25-dihydroxyvitamin NN 113 115 D3 d3 NN 116 118 in in IN 119 125 normal normal JJ 126 131 human human JJ 132 141 monocytes monocyte NNS 141 142 . . . 144 147 The the DT 148 155 genomic genomic JJ 156 163 actions action NNS 164 166 of of IN 167 188 1,25-dihydroxyvitamin 1,25-dihydroxyvitamin NN 189 191 D3 d3 NN 192 193 ( ( ( 193 205 1,25(OH)2D3) 1,25(oh)2d3) NN 206 209 are be VBP 210 218 mediated mediate VBN 219 221 by by IN 222 225 the the DT 226 239 intracellular intracellular JJ 240 247 vitamin vitamin NN 248 249 D D NNP 250 258 receptor receptor NN 259 260 ( ( ( 260 263 VDR VDR NNP 263 264 ) ) ) 264 265 . . . 266 274 Although although IN 275 294 immunocytochemistry immunocytochemistry NN 295 298 has have VBZ 299 304 shown show VBN 305 309 that that IN 310 320 disruption disruption NN 321 323 of of IN 324 336 microtubular microtubular JJ 337 345 assembly assembly NN 346 354 prevents prevent VBZ 355 362 nuclear nuclear JJ 363 369 access access NN 370 372 of of IN 373 376 the the DT 377 387 sterol-VDR sterol-VDR NNP 388 395 complex complex NN 395 396 , , , 397 400 the the DT 401 405 role role NN 406 408 of of IN 409 421 microtubules microtubule NNS 422 424 in in IN 425 428 the the DT 429 437 response response NN 438 440 to to TO 441 452 1,25(OH)2D3 1,25(OH)2D3 NNP 453 456 has have VBZ 457 460 not not RB 461 465 been be VBN 466 473 studied study VBN 474 476 in in IN 477 483 viable viable JJ 484 489 cells cell NNS 489 490 . . . 491 494 Our our PRP$ 495 502 studies study NNS 503 511 examined examine VBN 512 516 this this DT 517 528 interaction interaction NN 529 531 in in IN 532 538 normal normal JJ 539 544 human human JJ 545 554 monocytes monocyte NNS 554 555 . . . 556 565 Monocytes monocyte NNS 566 573 convert convert VBP 574 582 25(OH)D3 25(oh)d3 NN 583 585 to to TO 586 597 1,25(OH)2D3 1,25(oh)2d3 NN 598 601 and and CC 602 604 to to TO 605 620 24-hydroxylated 24-hydroxylate VBN 621 632 metabolites metabolite NNS 633 637 more more RBR 638 643 polar polar JJ 644 648 than than IN 649 660 1,25(OH)2D3 1,25(OH)2D3 NNP 660 661 . . . 662 673 Microtubule Microtubule NNP 674 684 disruption disruption NN 685 692 totally totally RB 693 702 abolished abolish VBD 703 706 the the DT 707 714 ability ability NN 715 717 of of IN 718 727 exogenous exogenous JJ 728 739 1,25(OH)2D3 1,25(oh)2d3 NN 740 742 to to TO 743 751 suppress suppress VB 752 755 its its PRP$ 756 759 own own JJ 760 769 synthesis synthesis NN 770 773 and and CC 774 776 to to TO 777 783 induce induce VB 784 798 24-hydroxylase 24-hydroxylase NN 799 803 mRNA mrna NN 804 807 and and CC 808 816 activity activity NN 816 817 , , , 818 825 without without IN 826 835 affecting affect VBG 836 842 either either CC 843 848 total total JJ 849 860 1,25(OH)2D3 1,25(oh)2d3 NN 861 867 uptake uptake NN 868 870 or or CC 871 878 maximal maximal JJ 879 894 1,25(OH)2D3-VDR 1,25(oh)2d3-vdr NN 895 902 binding binding NN 902 903 . . . 904 908 Thus thus RB 908 909 , , , 910 916 intact intact JJ 917 929 microtubules microtubule NNS 930 933 are be VBP 934 943 essential essential JJ 944 947 for for IN 948 969 1,25(OH)2D3-dependent 1,25(oh)2d3-dependent JJ 970 980 modulation modulation NN 981 983 of of IN 984 988 gene gene NN 989 1002 transcription transcription NN 1002 1003 . . . 1004 1017 Interestingly interestingly RB 1017 1018 , , , 1019 1030 microtubule microtubule NN 1031 1041 disruption disruption NN 1042 1046 also also RB 1047 1056 decreased decrease VBD 1057 1065 monocyte monocyte NN 1066 1077 1,25(OH)2D3 1,25(oh)2d3 NN 1078 1087 synthesis synthesis NN 1087 1088 , , , 1089 1092 not not RB 1093 1095 by by IN 1096 1106 decreasing decrease VBG 1107 1110 the the DT 1111 1115 Vmax Vmax NNP 1116 1118 of of IN 1119 1127 monocyte monocyte NN 1128 1141 mitochondrial mitochondrial JJ 1142 1143 1 1 CD 1144 1161 alpha-hydroxylase alpha-hydroxylase NN 1162 1165 but but CC 1166 1173 through through IN 1174 1176 an an DT 1177 1185 increase increase NN 1186 1188 in in IN 1189 1192 the the DT 1193 1195 Km Km NNP 1196 1199 for for IN 1200 1209 25(OH)2D3 25(OH)2D3 NNP 1209 1210 . . . 1211 1213 We we PRP 1214 1222 examined examine VBD 1223 1231 25(OH)D3 25(oh)d3 NN 1232 1241 transport transport NN 1241 1242 . . . 1243 1254 Microtubule Microtubule NNP 1255 1265 disruption disruption NN 1266 1269 did do VBD 1270 1273 not not RB 1274 1280 affect affect VB 1281 1286 total total JJ 1287 1295 cellular cellular JJ 1296 1304 25(OH)D3 25(oh)d3 NN 1305 1311 uptake uptake NN 1312 1315 but but CC 1316 1323 reduced reduce VBD 1324 1327 its its PRP$ 1328 1341 intracellular intracellular JJ 1342 1353 trafficking trafficking NN 1354 1356 to to TO 1357 1360 the the DT 1361 1373 mitochondria mitochondrion NNS 1373 1374 . . . 1375 1379 Thus thus RB 1379 1380 , , , 1381 1393 microtubules microtubule NNS 1394 1405 participate participate VBP 1406 1408 in in IN 1409 1422 intracellular intracellular JJ 1423 1431 25(OH)D3 25(oh)d3 NN 1432 1441 transport transport NN 1441 1442 , , , 1443 1446 and and CC 1447 1452 their their PRP$ 1453 1462 integrity integrity NN 1463 1473 determines determine VBZ 1474 1480 normal normal JJ 1481 1492 1,25(OH)2D3 1,25(oh)2d3 NN 1493 1502 synthesis synthesis NN 1502 1503 . . .